{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:53:15Z","timestamp":1781643195904,"version":"3.54.5"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2024ZD0529400"],"award-info":[{"award-number":["2024ZD0529400"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82573732"],"award-info":[{"award-number":["82573732"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China Major Joint Project on Key Scientific Issues of Lung Cancer","award":["82241235"],"award-info":[{"award-number":["82241235"]}]},{"name":"National High-Level Talents Special Support Program","award":["KA0120231004"],"award-info":[{"award-number":["KA0120231004"]}]},{"name":"Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Surg Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stage III non-small cell lung cancer (NSCLC) is heterogeneous and poses significant treatment challenges. In recent years, neoadjuvant therapy has emerged as a promising treatment strategy for patients with stage III NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report the case of a 39-year-old woman with stage IIIB lung adenocarcinoma harboring a neuroplastin-neuregulin 1 (NPTN\n                      <jats:bold>-<\/jats:bold>\n                      NRG1) fusion who achieved a dramatic response to neoadjuvant afatinib. After three months of therapy, imaging showed a partial response; the patient subsequently underwent complete surgical resection with an uneventful recovery and has remained disease-free to date. To explore the mechanism underlying this response, we performed single-cell RNA sequencing (scRNA-seq) and T-cell receptor (TCR) sequencing of tumor tissues and lymph nodes. The analysis revealed a mutual interaction between CD8\n                      <jats:sup>+<\/jats:sup>\n                      effector T cells, CD8\n                      <jats:sup>+<\/jats:sup>\n                      memory T cells, and natural killer-like (NK-like) T cells via C-C chemokine ligand (CCL)5-C-C chemokine receptor (CCR)5, CCL5-CCR3, and CCL5-CCR1 ligand-receptor pairs. These findings indicate that the post-treatment microenvironment is characterized by active chemokine signaling and immune cell crosstalk, which may contribute to the anti-tumor response.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This case highlights the efficacy of afatinib in the perioperative treatment of NSCLC with NRG1 fusion, and supports its potential as a personalized therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12957-026-04233-6","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T01:34:54Z","timestamp":1773452094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant afatinib in a patient with locally advanced lung adenocarcinoma harboring an NPTN-NRG1 fusion: a case report"],"prefix":"10.1186","volume":"24","author":[{"given":"Chu-Yu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Bin","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ji","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri-Qiang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Long","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Zhao","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"4233_CR1","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1158\/2159-8290.CD-13-0633","volume":"4","author":"L Fernandez-Cuesta","year":"2014","unstructured":"Fernandez-Cuesta L, Plenker D, Osada H, Sun R, Menon R, Leenders F, Ortiz-Cuaran S, Peifer M, Bos M, Da\u00dfler J, et al. CD74-NRG1 fusions in lung adenocarcinoma. Cancer Discov. 2014;4:415\u201322.","journal-title":"Cancer Discov"},{"key":"4233_CR2","doi-asserted-by":"crossref","unstructured":"Kucharczyk T, Nico\u015b M, Kucharczyk M, Kalinka E. NRG1 gene Fusions-What promise remains behind these rare genetic alterations? a comprehensive review of Biology, diagnostic Approaches, and clinical implications. Cancers (Basel). 2024;16:2766.","DOI":"10.3390\/cancers16152766"},{"key":"4233_CR3","doi-asserted-by":"crossref","unstructured":"Xu S, Lu Z. Exploring FNDC4 as a biomarker for prognosis and immunotherapy response in lung adenocarcinoma. Asian J Surg. 2024;48:1799-1801.","DOI":"10.1016\/j.asjsur.2024.09.054"},{"key":"4233_CR4","doi-asserted-by":"crossref","unstructured":"Xu S, Lu Z. The role of LMNB2 as a diagnostic and prognostic biomarker in lung adenocarcinoma. Asian J Surg. 2024;48:1175-77.","DOI":"10.1016\/j.asjsur.2024.08.056"},{"key":"4233_CR5","doi-asserted-by":"publisher","first-page":"e14635","DOI":"10.1200\/JCO.2024.42.16_suppl.e14635","volume":"42","author":"Z Lu","year":"2024","unstructured":"Lu Z, Xu S, Ye M, Shen T, Zhang X, Rao D, Chen J, Lin Z, Chang M, Xiong G, et al. Comparison of pembrolizumab plus chemotherapy versus concurrent or sequential radiochemotherapy in patients with driver mutation-lacking lung adenocarcinoma presenting with recurrent laryngeal nerve invasion leading to hoarseness. J Clin Oncol. 2024;42:e14635\u201314635.","journal-title":"J Clin Oncol"},{"key":"4233_CR6","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1016\/j.annonc.2020.08.2335","volume":"31","author":"J Laskin","year":"2020","unstructured":"Laskin J, Liu SV, Tolba K, Heining C, Schlenk RF, Cheema P, Cadranel J, Jones MR, Drilon A, Cseh A, et al. NRG1 fusion-driven tumors: biology, detection, and the therapeutic role of Afatinib and other ErbB-targeting agents. Ann Oncol. 2020;31:1693\u2013703.","journal-title":"Ann Oncol"},{"key":"4233_CR7","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.21037\/atm-21-3923","volume":"9","author":"X Wu","year":"2021","unstructured":"Wu X, Zhang D, Shi M, Wang F, Li Y, Lin Q. Successful targeting of the NRG1 fusion reveals durable response to Afatinib in lung adenocarcinoma: a case report. Ann Transl Med. 2021;9:1507.","journal-title":"Ann Transl Med"},{"key":"4233_CR8","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1186\/s12957-023-03129-z","volume":"21","author":"X Nie","year":"2023","unstructured":"Nie X, Zhang P, Bie Z, Song C, Zhang M, Ma D, Cui D, Cheng G, Li H, Lei Y, et al. Durable response to Afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report. World J Surg Oncol. 2023;21:246.","journal-title":"World J Surg Oncol"},{"key":"4233_CR9","doi-asserted-by":"publisher","first-page":"104545","DOI":"10.1016\/j.esmoop.2025.104545","volume":"10","author":"J Rodon","year":"2025","unstructured":"Rodon J, Rothe M, Mangat PK, Garrett-Mayer E, Cannon TL, Hobbs E, Kalemkerian GP, Hinshaw DC, Gregory A, Grantham GN, et al. Afatinib in patients with solid tumors with neuregulin 1 (NRG1) fusions: a case series from the targeted agent and profiling utilization registry (TAPUR) study. ESMO Open. 2025;10:104545.","journal-title":"ESMO Open"},{"key":"4233_CR10","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1016\/j.jtho.2023.07.006","volume":"18","author":"JM Lee","year":"2023","unstructured":"Lee JM, McNamee CJ, Toloza E, Negrao MV, Lin J, Shum E, Cummings AL, Kris MG, Sepesi B, Bara I, et al. Neoadjuvant targeted therapy in resectable NSCLC: current and future perspectives. J Thorac Oncol. 2023;18:1458\u201377.","journal-title":"J Thorac Oncol"},{"key":"4233_CR11","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.21037\/tlcr-24-359","volume":"13","author":"M Kemper","year":"2024","unstructured":"Kemper M, Elges S, Kies P, Wiebe K, Lenz G, Bleckmann A, Evers G. What do we know about the role of neoadjuvant targeted therapy in early-stage EGFR-mutant and ALK-fused non-small cell lung cancer?-a narrative review of the current literature. Transl Lung Cancer Res. 2024;13:2813\u201327.","journal-title":"Transl Lung Cancer Res"},{"key":"4233_CR12","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1200\/JCO-25-00883","volume":"43","author":"J He","year":"2025","unstructured":"He J, Tsuboi M, Weder W, Chen KN, Hochmair MJ, Shih JY, Lee SY, Lee KY, Nhung NV, Saeteng S, et al. Neoadjuvant osimertinib for resectable EGFR-Mutated Non-Small cell lung cancer. J Clin Oncol. 2025;43:2875\u201387.","journal-title":"J Clin Oncol"},{"key":"4233_CR13","doi-asserted-by":"publisher","first-page":"4655","DOI":"10.1038\/s41467-023-40349-z","volume":"14","author":"D Bian","year":"2023","unstructured":"Bian D, Sun L, Hu J, Duan L, Xia H, Zhu X, Sun F, Zhang L, Yu H, Xiong Y, et al. Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study. Nat Commun. 2023;14:4655.","journal-title":"Nat Commun"},{"key":"4233_CR14","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1200\/JCO.20.03307","volume":"39","author":"A Drilon","year":"2021","unstructured":"Drilon A, Duruisseaux M, Han JY, Ito M, Falcon C, Yang SR, Murciano-Goroff YR, Chen H, Okada M, Molina MA, et al. Clinicopathologic features and response to therapy of NRG1 Fusion-Driven lung cancers: the eNRGy1 global multicenter registry. J Clin Oncol. 2021;39:2791\u2013802.","journal-title":"J Clin Oncol"},{"key":"4233_CR15","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1200\/JCO.19.00075","volume":"37","author":"WZ Zhong","year":"2019","unstructured":"Zhong WZ, Chen KN, Chen C, Gu CD, Wang J, Yang XN, Mao WM, Wang Q, Qiao GB, Cheng Y, et al. Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-Mutant Non-Small-Cell lung cancer (EMERGING-CTONG 1103): A randomized phase II study. J Clin Oncol. 2019;37:2235\u201345.","journal-title":"J Clin Oncol"},{"key":"4233_CR16","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.lungcan.2023.02.011","volume":"178","author":"C Lv","year":"2023","unstructured":"Lv C, Fang W, Wu N, Jiao W, Xu S, Ma H, Wang J, Wang R, Ji C, Li S, et al. Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial. Lung Cancer. 2023;178:151\u20136.","journal-title":"Lung Cancer"},{"key":"4233_CR17","doi-asserted-by":"publisher","first-page":"834731","DOI":"10.3389\/fgene.2022.834731","volume":"13","author":"S Xu","year":"2022","unstructured":"Xu S, Liu Y, Ma H, Fang S, Wei S, Li X, Lu Z, Zheng Y, Liu T, Zhu X, et al. A novel signature integrated of Immunoglobulin, glycosylation and Anti-Viral genes to predict prognosis for breast cancer. Front Genet. 2022;13:834731.","journal-title":"Front Genet"},{"key":"4233_CR18","doi-asserted-by":"crossref","unstructured":"Wang P, Xu S, Guo Q, Zhao Y. Discovery of PAK2 as a Key Regulator of Cancer Stem Cell in Head and Neck Squamous Cell Carcinoma Using Multi-Omic Techniques. Stem Cells Int. 2025;2025:1325262.","DOI":"10.1155\/sci\/1325262"},{"key":"4233_CR19","doi-asserted-by":"publisher","first-page":"1678907","DOI":"10.3389\/fimmu.2025.1678907","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang Y, Lu K, Xu Y, Xu S, Chu H, Fang X. Antibody-drug conjugates as immuno-oncology agents in colorectal cancer: targets, payloads, and therapeutic synergies. Front Immunol. 2025;16:1678907.","journal-title":"Front Immunol"},{"key":"4233_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41698-021-00181-4","volume":"5","author":"NJ Gurule","year":"2021","unstructured":"Gurule NJ, McCoach CE, Hinz TK, Merrick DT, Van Bokhoven A, Kim J, Patil T, Calhoun J, Nemenoff RA, Tan AC, et al. A tyrosine kinase inhibitor-induced interferon response positively associates with clinical response in EGFR-mutant lung cancer. NPJ Precis Oncol. 2021;5:41.","journal-title":"NPJ Precis Oncol"}],"container-title":["World Journal of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12957-026-04233-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12957-026-04233-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12957-026-04233-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:03:02Z","timestamp":1781640182000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12957-026-04233-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,14]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4233"],"URL":"https:\/\/doi.org\/10.1186\/s12957-026-04233-6","relation":{},"ISSN":["1477-7819"],"issn-type":[{"value":"1477-7819","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,14]]},"assertion":[{"value":"24 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declartions"}},{"value":"The research followed the principles outlined in the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Board of Guangdong Provincial People\u2019s Hospital (No. KY2025-054-01).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The patient provided written consent for the publication of this case report and any related images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"192"}}